Prostate cancer is the second leading cause of cancer mortality in American men. The long-term objective of this research is to develop novel multimodality molecular imaging techniques for improved early detection and image-guided therapy for prostate cancer. At our institution, a second generation photosensitizing drug PC 4 has been evaluated for photodynamic therapy (PDT) at the Case Comprehensive Cancer Center. This drug is currently undergoing pre-clinical mechanistic studies and two Phase I clinical trials for the treatment of dermal cancers, including cancers that are metastatic to the skin. Members of this investigating team have already proven the efficacy of PC 4-PDT for the treatment of breast, ovarian, and colon cancer in animal models. In addition, a co-investigator, Dr. Nancy Oleinick found that PC 4-PDT induces apoptosis in prostate cancer cells in vitro. We are now extending this relatively new treatment modality for prostate cancer therapy. In the R21 phase, we will perform in vivo PDT to treat human prostate cancer xenografts in a mouse model. State-of-the-art in vivo molecular imaging techniques will be developed to assess the PDT efficacy. Image fusion and registration of various imaging modalities and quantitative image analysis methods will be developed to combine functional biochemical images with high-resolution anatomic images. An early image-based surrogate biomarker of the tumor response to PDT will be identified to predict the success of the therapy. The noninvasive imaging techniques to be created from this study can be applied to other cancers. They can be used to detect very early cancers, optimize treatment planning for individualized therapy, utilize image-guided minimally invasive therapy, and monitor the therapeutic efficacy. The proposed imaging strategy has great potential to enhance public health by improving diagnosis and therapy of cancer.